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Melanocortin 4 Rece...
Melanocortin 4 Receptor Constitutive Activity Inhibits L-Type Voltage-Gated Calcium Channels In Neurons
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- Agosti, F. (författare)
- Uppsala universitet,Funktionell farmakologi,Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.
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- Cordisco Gonzalez, S. (författare)
- Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.
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- Martinez Damonte, V. (författare)
- Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.
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- Tolosa, M. J. (författare)
- Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.
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- Di Siervi, N. (författare)
- Univ Buenos Aires, CONICET, ININFA, Inst Invest Farmacol, Buenos Aires, DF, Argentina.
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- Schiöth, Helgi B. (författare)
- Uppsala universitet,Funktionell farmakologi
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- Davio, C. (författare)
- Univ Buenos Aires, CONICET, ININFA, Inst Invest Farmacol, Buenos Aires, DF, Argentina.
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- Perello, M. (författare)
- CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.;Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol, IMBICE,Neurophysiol Lab, La Plata, Buenos Aires, Argentina.
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- Raingo, J. (författare)
- Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.
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(creator_code:org_t)
- PERGAMON-ELSEVIER SCIENCE LTD, 2017
- 2017
- Engelska.
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Ingår i: Neuroscience. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4522 .- 1873-7544. ; 346, s. 102-112
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (Ca(V)2.2) are inhibited by MC4R agonist-dependent activation, while the Ca-V subtypes that carry L- and P/Q-type current are not. Here, we tested the hypothesis that MC4R constitutive activity can affect Ca-V, with focus on the channel subtypes that can control transcriptional activity coupled to depolarization (L-type, Ca(V)1.2/1.3) and neurotransmitter release (N- and P/Q-type, Ca(V)2.2 and Ca(V)2.1). We found that MC4R constitutive activity inhibits specifically Ca(V)1.2/1.3 and Ca(V)2.1 subtypes of Ca-V. We also explored the signaling pathways mediating this inhibition, and thus propose that agonist-dependent and basal MC4R activation modes signal differentially through G(s) and G(i/o) pathways to impact on different Ca-V subtypes. In addition, we found that chronic incubation with MC4R endogenous inverse agonist, agouti and agouti-related peptide (AgRP), occludes Ca-V inhibition in a cell line and in amygdaloid complex cultured neurons as well. Thus, we define new mechanisms of control of the main mediators of depolarization-induced calcium entry into neurons by a GPCR that displays constitutive activity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- calcium channels
- melanocortin receptor
- electrophysiology
- G protein
- amygdala
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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